You have all heard about the DNA double helix and genes. Many of you know that mutations occur randomly, that the DNA sequence is read by successive groups of three bases (the codons), that many genes encode enzymes, and that gene expression can be regulated.
These concepts were proposed on the basis of astute genetic experiments, as well as often on biochemical results. The original articles were these concepts appeared are however not frequently part of the normal curriculum of biologists, biochemists and medical students.
This course proposes to read study and discuss a small selection of these classical papers, and to put these landmarks in their historical context. Most of the authors displayed interesting personal histories and many of their contributions go beyond not only the papers we will read but probably all their scientific papers.
Our understanding of the scientific process, of the philosophy underlying the process of scientific discovery, and on the integration of new concepts is not only important for the history of science but also for the mental development of creative science.

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Session 11

The major start point in the modern history of lysogeny, written by Lwoff and Guttman, is not available in English. We will start this session with the study by Bertani of the Li strain of E. coli that carries 3 lysogenic prophages. Each prophage can be induced independently of the other two, and the relative rate of spontaneous induction depends on the physiological state of the cells. Bertani devised a method for detecting single bursts and could calculate that the rate of induction is about 1 per 50000 cells per generation, a rate much lower that that observed by Lwoff with the B. megatherium prophage.After a brief outline of the regulation of phage lambda, we will discuss the lethal phenotype of a thermo-inducible prophage that cannot excise from the chromosome. Suppressors of this phenotype belong to two main classes: mutations in genes O or P prevent phage replication while x mutations prevent the expression of the early operon that includes O and P. Upon shift to the high temperature, the repressor becomes inactivated. If the cells are incubated at the high temperature for several generations and returned to the permissive temperature where the repressor can be active, the x mutants do slowly recover immunity while the O and P mutants remain permanently non immune. We now know that x mutations inactivate an early operon that contains O and P. These mutations have been called “physiological deletions”. The phenotype of the x mutants is recessive, providing the first evidence for cro, a new gene in the x-O-P operon. Mutants that do not make Cro have been isolated. Unlike wild type phage that preferentially turn on the lytic program, cro mutants are unable to form plaques because lysogeny is the preferential program. Cro also represses the other early operon since its expression is increased with both x and cro mutants